U.S. patent number 11,226,274 [Application Number 15/043,332] was granted by the patent office on 2022-01-18 for method of analyzing using analyte concentrator system having eluent generation module.
This patent grant is currently assigned to DIONEX CORPORATION. The grantee listed for this patent is DIONEX CORPORATION. Invention is credited to Kannan Srinivasan.
United States Patent |
11,226,274 |
Srinivasan |
January 18, 2022 |
Method of analyzing using analyte concentrator system having eluent
generation module
Abstract
Systems and methods for concentrating an analyte preparatory to
analysis thereof include processing the effluent of an analyte
concentrator to produce an eluent for eluting an analyte retained
in the same or separate concentrator, and systems implementing the
same. The analyte concentrator system connects the effluent outlet
of an analyte concentrator column to an eluent generation module
such that the substantially analyte-free effluent discharged from
the analyte concentrator column passes fluidly into the eluent
generation module. Eluent generated from the substantially
analyte-free effluent in the eluent generation module is likewise
substantially free of the analyte. The systems and methods can
minimize and/or (substantially) eliminate background signal during
analysis of the concentrated analyte.
Inventors: |
Srinivasan; Kannan (Tracy,
CA) |
Applicant: |
Name |
City |
State |
Country |
Type |
DIONEX CORPORATION |
Sunnyvale |
CA |
US |
|
|
Assignee: |
DIONEX CORPORATION (Sunnyvale,
CA)
|
Family
ID: |
1000006058622 |
Appl.
No.: |
15/043,332 |
Filed: |
February 12, 2016 |
Prior Publication Data
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|
|
Document
Identifier |
Publication Date |
|
US 20170234782 A1 |
Aug 17, 2017 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
G01N
30/08 (20130101); B01D 15/361 (20130101); G01N
30/38 (20130101); G01N 30/96 (20130101); G01N
1/405 (20130101); G01N 30/40 (20130101); G01N
2030/085 (20130101) |
Current International
Class: |
G01N
1/40 (20060101); G01N 30/08 (20060101); G01N
30/96 (20060101); G01N 30/38 (20060101); G01N
30/40 (20060101); B01D 15/36 (20060101) |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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0038720 |
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Oct 1981 |
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EP |
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H09511838 |
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Nov 1997 |
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JP |
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2001520752 |
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Oct 2001 |
|
JP |
|
9627793 |
|
Sep 1996 |
|
WO |
|
9938595 |
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Aug 1999 |
|
WO |
|
Other References
Dionex Technical Note 8: The Use of Concentrator Columns in Ion
Chromatography. Dionex Corporation, Sunnyvale, CA. 1994 (Year:
1994). cited by examiner .
Dionex. "Reagent-Free Ion Chromatography Systems with Eluent
Regeneration," Dionex Corporation, Sunnyvale, CA. LPN 2022-03 PDF
3/10. (Year: 2010). cited by examiner .
Bruno et al., "Determination of nutrients in the presence of high
chloride concentrations by column-switching ion chromatography," J.
of Chrom. A, 1003, 133-141, 2003. cited by applicant .
Christison et al., "Determination of Trace Anions in Ultrapure
Water Using Capillary Ion Chromatography," Technical Note: 112, 11
pages, 2012. cited by applicant .
Colombini et al., "Use of column-switching ion chromatography for
the simultaneous determination of total nitrogen and phosphorus
after microwave assisted persulphate digestion," J. of Chrom. A,
822, 162-166, 1998. cited by applicant .
Galceran et al., "Column-switching techniques in the analysis of
phosphate by ion chromatography," J. Chrom. A, 675, 141-147, 1994.
cited by applicant .
Huang et al., "Determination of Bromate in Drinking Water at the
Low ug/L Level by Column Switching Ion Chromatography," J. Liq.
Chrom. & Rel. Technol., 22(14), 2235-2245, 1999. cited by
applicant .
Peldszus et al., "Quantitative determination of oxalate and other
organic acids in drinking water at low ug/l concentrations," J.
Chrom. A, 793, 198-203, 1998. cited by applicant .
Rey et al., "Column switching for difficult cation separations," J.
Chrom. A, 789, 149-155, 1997. cited by applicant .
Umile et al., "Significant reduction of the detection limit in ion
chromatography by relative analyte enrichment with column
switching," J. Chrom. A, 723, 11-17, 1996. cited by applicant .
Utzman et al., "Fast analysis of pulping liquors using ion
chromatography and col. switching," LC-GC 9(4), 301-302, 1991.
cited by applicant .
Villasenor, "Matrix Elimination in Liquid Chromatography Using
Heart-Cut Column Switching Techniques," Anal. Chem., 63, 1362-1366,
1991. cited by applicant .
Anonymous: "A Recent Development in Ion Chromatography Detection:
The Self-Regenerating Suppressor", International Laboratory, vol.
23, No. 1, Jan. 1993 (Jan. 1993), XP000354918, pp. 1-6, ISSN:
0010-2164. cited by applicant .
Biesaga M., et al., "Coupled Ion Chromatography for the
Determination of Chloride, Phosphate and Sulphate in Concentrated
Nitric Acid", Journal of Chromatography A, Elsevier, Amsterdam, NL,
vol. 1026, No. 1-2, Feb. 13, 2004 (Feb. 13, 2004), XP004482729, pp.
195-200, ISSN: 0021-9673. DOI: 10.1016/J.CHROMA.2003.11.001. cited
by applicant .
DIONEX Corporation, "The Use of Concentrator Columns in Ion
Chromatography", Technical Note 8, LPN0576, (1994), pp. 1-8. cited
by applicant .
Lui et al., "Reagent-free ion chromatography systems with eluent
regeneration: RFIC-ER systems", American Laboratory (2007), vol. 39
(3), pp. 17-19, 14. cited by applicant.
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Primary Examiner: Hixson; Christopher Adam
Assistant Examiner: Adams; Michelle
Attorney, Agent or Firm: Schell; David A. Ohara; Tim
Claims
What is claimed is:
1. A method of analyzing a fluid sample, comprising: processing a
fluid sample comprising an analyte in an analyte concentrator
system, the analyte concentrator system comprising a multi-port
valve and an analyte concentrator, the multi-port valve having a
plurality of ports including a first port fluidly coupled to a port
of the analyte concentrator, a second port fluidly coupled to
another port of the analyte concentrator, a third port fluidly
coupled to an inlet of an eluent generation module, and a fourth
port fluidly coupled to an outlet of the eluent generation module,
the multi-port valve having a first valve configuration and a
second valve configuration, wherein processing the fluid sample
comprises retaining the analyte in the analyte concentrator and
discharging from the analyte concentrator an effluent of the fluid
sample that is substantially free of the analyte, and wherein the
multi-port valve is in the first valve configuration during
processing the fluid sample to provide a first fluid flow path from
the analyte concentrator to the eluent generation module and a
second fluid flow path to the multi-port valve via the fourth port
from the eluent generation module; the second flow path bypassing
the analyte concentrator; in the eluent generation module,
generating an eluent from the discharged effluent, the generated
eluent being chemically configured to elute a portion of the
analyte retained in the analyte concentrator and the eluent being
substantially free of the analyte, wherein the generating the
eluent from the discharged effluent comprises passing the
discharged effluent into the eluent generation module, the eluent
generation module including an anode, a cathode, and an
electrolytic chamber disposed at least partially between the anode
and the cathode, the electrolytic chamber including an electrolyte
reservoir, an eluent generation chamber and at last ion exchange
connector, the electrolyte reservoir separated from eluent
generation chamber by the ion exchange connector, wherein the
passing the discharged effluent into the eluent generation module
comprises passing the discharged effluent through the multi-port
valve in the first valve configuration; switching the multi-port
valve from the first valve configuration to the second valve
configuration to provide a third fluid flow path from the eluent
generation module to the analyte concentrator; with the multi-port
valve in the second valve configuration, passing the eluent
generated in the eluent generation module into the analyte
concentrator system and eluting the portion of the analyte retained
in the analyte concentrator with the eluent, wherein the analyte
comprises at least one charged molecule or compound and the analyte
concentrator comprises an ion exchange element configured to retain
the at least one charged molecule or compound under a first ionic
strength and to release the at least one charged molecule or
compound under a second ionic strength; passing the eluted portion
of the analyte through a chromatography member to separate the
eluted portion of the analyte into individual components or
fractions, the chromatography member being fluidly coupled with the
analyte concentrator system via the multi-port valve; and passing
the individual components or fractions from the chromatography
member to an analyte detector for detecting the individual
components or fractions.
2. The method of claim 1, comprising passing the eluent in the
eluent generation module into the analyte concentrator system
through a fluid coupling extending between the eluent generation
module and the analyte concentrator system so as to elute the
portion of the analyte retained in the analyte concentrator with
the eluent.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
Not applicable.
BACKGROUND
1. Technical Field
The present disclosure relates generally to systems and methods for
concentrating an analyte preparatory to analysis thereof. In
particular, the present disclosure relates to methods for
processing the effluent of an analyte concentrator to produce an
eluent for eluting the analyte retained in the same or separate
concentrator, and to systems implementing the same. The present
disclosure further relates to an analyte concentrator system that
connects the effluent outlet of an analyte concentrator to an
eluent generation module, and to methods implementing the same.
2. Related Technology
In existing analyte concentrator systems (or columns), a fluid
sample containing at least one analyte molecule of interest is
introduced into an analyte concentrator column that retains at
least some of the analyte molecules in the fluid sample. After
washing any un-retained fluid sample or constituents thereof from
the column, the retained analyte molecules are eluted from the
column in a concentrated volume relative to the original fluid
sample. For instance, an eluent having a chemical composition
adapted for eluting the retained analyte molecules can be
introduced into the column to elute the retained analyte. In this
way, a fluid sample having a low concentration of analyte molecules
can be concentrated for more robust analysis of the analyte.
FIG. 1 is a flowchart diagram illustrating a prior art analyte
concentrator system 8 as known to those skilled in the art. As
depicted in FIG. 1, an analyte sample 10 is introduced via input
line 12 into an analyte concentrator 14. Analyte concentrator 14 is
configured to retain one or more analyte molecules of interest
contained in analyte sample 10. Accordingly, the analyte is
retained in analyte concentrator 14, while the fluid sample
effluent is discharged via output line 16 to waste 18.
A wash fluid 20 may also be optionally introduced via input line 22
into analyte concentrator 14. Wash fluid 20 is configured to remove
any un-retained sample (e.g., sample fluid or molecular component
thereof) from analyte concentrator 14. The wash effluent is also
discharged via output line 16 to waste 18.
After washing analyte concentrator 14, an eluent 24 is introduced
into analyte concentrator 14. Eluent 24 is chemically configured to
elute the analyte retained in analyte concentrator 14. The eluted
analyte molecules of interest are then discharged from analyte
concentrator 14 (as a concentrated analyte sample) via output line
28 and introduced into analyte detector 30 for analysis.
One drawback to prior art system 8 and other existing concentrator
systems is the presence of analyte molecules and/or contaminants in
the wash fluid 20 and/or the eluent 24. Indeed, the wash fluid 20
and/or eluent 24 may include the very analyte sought to be analyzed
in analyte detector 30. Even wash fluid and/or eluent generated
from ultra-pure or nano-filtered water may not be entirely or even
substantially free of the analyte molecules of interest. Thus, the
amount or concentration of analyte eluted from analyte concentrator
14 may not represent the actual amount of analyte in analyte sample
10. Instead, analyte concentrator 14 may have retained the analyte
molecules contained in wash fluid 20. In addition, the eluent
itself may include analyte molecules; adding to the amount of
analyte molecules present in the eluted analyte sample. Further,
the eluent may include ionic contaminants from the water source
that interfere with the analyte measurement. These additional
sources of analyte molecules in the concentrated analyte sample can
adulterate the sample and alter the analytical results.
Subtractive normalization or other techniques may be used to remove
analytical (background) noise caused by analyte or ionic
contaminants in the eluent and/or wash fluid. However, if the
analyte sample only contained trace amounts (e.g., on the order of
parts-per-billion (ppb) or even parts-per-trillion (ppt)) of the
analyte molecules of interest, the background signal (or noise)
from the additional analyte molecules in the eluent and/or wash
fluid may overwhelm the analyte signal and negate accurate,
quantitative measurement of the concentrated analyte molecules of
interest.
Accordingly, it would be beneficial to provide systems and methods
for concentrating an analyte using a eluent that is substantially
free of the analyte molecule(s) of interest or ionic contaminants
(e.g., to minimize and/or (substantially) eliminate background
signal during analysis of the concentrated analyte).
BRIEF DESCRIPTION OF THE DRAWINGS
In order to describe the manner in which the above-recited and
other advantages and features of the invention can be obtained, or
to further clarify the above and other advantages and features of
the present disclosure, a more particular description of the
disclosure briefly described above will be rendered by reference to
specific implementations and/or embodiments thereof which are
illustrated in the appended drawings. While the drawings are
generally drawn to scale for some example embodiments, it should be
understood that the scale may be varied and the illustrated
embodiments are not necessarily drawn to scale for all embodiments
encompassed herein.
Furthermore, it will be readily appreciated that the components of
the illustrative embodiments, as generally described and
illustrated in the figures herein, could be arranged and designed
in a wide variety of different configurations, and that components
within some figures are interchangeable with, or may supplement,
features and components illustrated in other figures. Accordingly,
understanding that the drawings depict only typical implementations
and/or embodiments of the disclosure and are not, therefore, to be
considered to be limiting of its scope, the embodiments will be
described and explained with additional specificity and detail
through the use of the accompanying drawings in which:
FIG. 1 illustrates a schematic flow diagram of an exemplary prior
art system;
FIG. 2 illustrates a schematic flow diagram of an analyte
concentrator system in accordance with an embodiment of the present
disclosure;
FIG. 3 illustrates a schematic diagram of an analyte concentrator
assembly useful in the analyte concentrator system of FIG. 2 in
accordance with an embodiment of the present disclosure;
FIGS. 4A and 4B illustrate, respectively, schematic diagrams of an
analyte concentrator assembly in a first (4A) and second (4B)
configuration in accordance with an embodiment of the present
disclosure;
FIGS. 5A and 5B illustrate, respectively, schematic diagrams of an
analyte concentrator system in a first (5A) and second (5B)
configuration in accordance with another embodiment of the present
disclosure;
FIGS. 6A and 6B illustrate, respectively, schematic diagrams of an
analyte concentrator assembly in a first (6A) and second (6B)
configuration in accordance with another embodiment of the present
disclosure;
FIG. 7 illustrates an exemplary eluent generation module in
accordance with another embodiment of the present disclosure;
and
FIG. 8 illustrates an exemplary analyte detection module in
accordance with another embodiment of the present disclosure.
DETAILED DESCRIPTION
Before describing the present disclosure in detail, it is to be
understood that this disclosure is not limited to the specific
parameters of the particularly exemplified systems, methods,
apparatus, assemblies, products, processes, and/or kits, which may,
of course, vary. It is also to be understood that much, if not all
of the terminology used herein is only for the purpose of
describing particular embodiments of the present disclosure, and is
not necessarily intended to limit the scope of the disclosure in
any particular manner. Thus, while the present disclosure will be
described in detail with reference to specific configurations,
embodiments, and/or implementations thereof, the descriptions are
illustrative only and are not to be construed as limiting the scope
of the claimed invention.
Various aspects of the present disclosure, including devices,
systems, methods, etc., may be illustrated with reference to one or
more exemplary embodiments or implementations. As used herein, the
terms "exemplary embodiment" and/or "exemplary implementation"
means "serving as an example, instance, or illustration," and
should not necessarily be construed as preferred or advantageous
over other embodiments or implementations disclosed herein. In
addition, reference to an "implementation" of the present
disclosure or invention includes a specific reference to one or
more embodiments thereof, and vice versa, and is intended to
provide illustrative examples without limiting the scope of the
invention, which is indicated by the appended claims rather than by
the following description.
Furthermore, unless defined otherwise, all technical and scientific
terms used herein have the same meaning as commonly understood by
one of ordinary skill in the art to which the present disclosure
pertains. While a number of methods and materials similar or
equivalent to those described herein can be used in the practice of
the present disclosure, only certain exemplary materials and
methods are described herein.
It will be noted that, as used in this specification and the
appended claims, the singular forms "a," "an" and "the" include
plural referents unless the content clearly dictates otherwise.
Thus, for example, reference to a "column" includes one, two, or
more columns. Similarly, reference to a plurality of referents
should be interpreted as comprising a single referent and/or a
plurality of referents unless the content and/or context clearly
dictate otherwise. Thus, reference to "columns" does not
necessarily require a plurality of such columns. Instead, it will
be appreciated that independent of conjugation; one or more columns
are contemplated herein.
As used throughout this application the words "can" and "may" are
used in a permissive sense (i.e., meaning having the potential to),
rather than the mandatory sense (i.e., meaning must). Additionally,
the terms "including," "having," "involving," "containing,"
"characterized by," as well as variants thereof (e.g., "includes,"
"has," and "involves," "contains," etc.), and similar terms as used
herein, including the claims, shall be inclusive and/or open-ended,
shall have the same meaning as the word "comprising" and variants
thereof (e.g., "comprise" and "comprises"), and do not exclude
additional, un-recited elements or method steps,
illustratively.
Various aspects of the present disclosure can be illustrated by
describing components that are coupled, attached, connected, and/or
joined together. As used herein, the terms "coupled", "attached",
"connected," and/or "joined" are used to indicate either a direct
association between two components or, where appropriate, an
indirect association with one another through intervening or
intermediate components. In contrast, when a component is referred
to as being "directly coupled", "directly attached", "directly
connected," and/or "directly joined" to another component, no
intervening elements are present or contemplated. Thus, as used
herein, the terms "connection," "connected," and the like do not
necessarily imply direct contact between the two or more elements.
In addition, components that are coupled, attached, connected,
and/or joined together are not necessarily (reversibly or
permanently) secured to one another. For instance, coupling,
attaching, connecting, and/or joining can comprise placing,
positioning, and/or disposing the components together or otherwise
adjacent in some implementations.
As used herein, directional and/or arbitrary terms, such as "top,"
"bottom," "front," "back," "rear," "left," "right," "up," "down,"
"upper," "lower," "inner," "outer," "internal," "external,"
"interior," "exterior," "proximal," "distal," and the like can be
used solely to indicate relative directions and/or orientations and
may not otherwise be intended to limit the scope of the disclosure,
including the specification, invention, and/or claims.
To facilitate understanding, like reference numerals have been
used, where possible, to designate like elements common to the
figures. Furthermore, alternative configurations of a particular
element may each include separate letters appended to the element
number. Accordingly, an appended letter can be used to designate an
alternative design, structure, function, implementation, and/or
embodiment of an element or feature without an appended letter.
Similarly, multiple instances of an element and or sub-elements of
a parent element may each include separate letters appended to the
element number. In each case, the element label may be used without
an appended letter to generally refer to instances of the element
or any one of the alternative elements. Element labels including an
appended letter can be used to refer to a specific instance of the
element or to distinguish or draw attention to multiple uses of the
element. However, element labels including an appended letter are
not meant to be limited to the specific and/or particular
embodiment(s) in which they are illustrated. In other words,
reference to a specific feature in relation to one embodiment
should not be construed as being limited to applications only
within said embodiment.
It will also be appreciated that where two or more values, or a
range of values (e.g., less than, greater than, at least, and/or up
to a certain value, and/or between two recited values) is disclosed
or recited, any specific value or range of values falling within
the disclosed values or range of values is likewise disclosed and
contemplated herein. Thus, disclosure of an illustrative
measurement or distance less than or equal to about 10 units or
between 0 and 10 units includes, illustratively, a specific
disclosure of: (i) a measurement of 9 units, 5 units, 1 units, or
any other value between 0 and 10 units, including 0 units and/or 10
units; and/or (ii) a measurement between 9 units and 1 units,
between 8 units and 2 units, between 6 units and 4 units, and/or
any other range of values between 0 and 10 units.
Various modifications can be made to the illustrated embodiments
without departing from the spirit and scope of the invention as
defined by the claims. Thus, while various aspects and embodiments
have been disclosed herein, other aspects and embodiments are
contemplated. It is also noted that systems, methods, apparatus,
devices, products, processes, and/or kits, etc., according to
certain embodiments of the present disclosure may include,
incorporate, or otherwise comprise properties, features,
components, members, and/or elements described in other embodiments
disclosed and/or described herein. Thus, reference to a specific
feature in relation to one embodiment should not be construed as
being limited to applications only within said embodiment.
The headings used herein are for organizational purposes only and
are not meant to be used to limit the scope of the description or
the claims.
In the description, example systems, methods, and/or apparatus may
be described with reference to one or more analytes or analyte
molecules (of interest). It should be appreciated that as used
herein, "analyte" can refer to a substance whose chemical
constituent(s) are being analyzed (e.g., detected, isolated,
separated, identified, measured, quantified, etc.) and/or the
chemical constituent(s) themselves (i.e., a chemical substance that
is the subject of chemical analysis, a substance or chemical
constituent that is of interest in an analytical procedure, etc.).
Thus, an illustrative fluid (e.g., drinking water) sample can be
and/or constitute an analyte having or comprising one or more
analyte molecules of interest disposed or contained therein.
Alternatively or in addition, the one or more analyte molecules of
interest disposed or contained in the drinking water sample can
likewise constitute analyte(s). Thus, where appropriate, an analyte
(i.e., fluid sample) can be introduced into a concentrator column
configured to retain the analyte (i.e., molecule(s) of interest)
without departing from the scope of this disclosure.
Moreover, as used herein, a "molecule" or "molecule of interest"
includes other matter of interest, including but not limited to
cells, particles, compounds, crystals, aggregates, etc. For
instance, in at least one embodiment, a molecule of interest can
comprise phosphate, sulfate, nitrate, nitride, bromate, chlorite,
chloroform, bromoform, asbestos, or another molecular compound,
including acids, hydrocarbons, and the like. In other embodiments,
a molecule of interest can comprise a (charged) elemental molecule,
such as fluoride, chloride, bromide, arsenic, barium, chromium,
etc., as well as compounds including the same. Thus, reference to a
"molecule" or "molecule of interest" should not be construed as
being limited to a (single) molecule, per se. Rather, such terms
should be construed broadly to include any substance or matter
(e.g., that may be present or included in a liquid sample).
In addition, example systems, methods, and/or apparatus may be
described with reference to one or more ions, ionic molecules,
ionized molecules, charged molecules, and the like. It will be
appreciated that such terms are illustrative and/or representative
of analytes, in general, and should be understood accordingly.
It is further to be understood that some of the drawings included
herewith, and which are referenced herein, are diagrammatic and
schematic representations of example embodiments, and are not
limiting of the present disclosure. Moreover, while various
drawings are provided at a scale that is considered functional for
some embodiments, the drawings are not necessarily drawn to scale
for all contemplated embodiments. No inference should therefore be
drawn from the drawings as to the necessity of any scale.
Furthermore, as indicated above, in the exemplary embodiments
illustrated in the figures, like structures will be provided with
similar reference designations, where possible. Specific language
will be used herein to describe the exemplary embodiments.
Nevertheless it will be understood that no limitation of the scope
of the disclosure is thereby intended. It is to be understood that
the drawings are diagrammatic and schematic representations of
various embodiments of this disclosure, and are not to be construed
as limiting the scope of the disclosure, unless such shape, form,
scale, function, or other feature is expressly described herein as
essential.
Alterations and further modifications of the inventive features
illustrated herein, and additional applications of the principles
illustrated herein, which would occur to one skilled in the
relevant art and having possession of this disclosure, are to be
considered within the scope of this disclosure. Unless a feature is
described as requiring another feature in combination therewith,
any feature herein may be combined with another feature of a same
or different embodiment disclosed herein. Furthermore, various
well-known aspects of illustrative systems, methods, apparatus, and
the like are not described herein in particular detail in order to
avoid obscuring aspects of the example embodiments.
Exemplary embodiments of the present disclosure generally relate to
systems and methods for concentrating an analyte preparatory for
analysis thereof. In particular, the present disclosure relates to
methods for processing the effluent of an analyte concentrator to
produce an eluent for eluting an analyte retained in the same or
separate concentrator, and to systems implementing the same. The
present disclosure further relates to an analyte concentrator
system that connects the effluent outlet of an analyte concentrator
to an eluent generation module, and to methods implementing the
same.
Reference will now be made to the figures to describe various
aspects of example embodiments of the disclosure. FIG. 2 depicts a
flow diagram of an analyte concentrator system 50 incorporating
some features of the present disclosure. In a first embodiment,
analyte concentrator system 50 comprises an analyte concentrator
assembly 56 fluid-coupled to an eluent generation module 64 via an
(effluent) output line 62. As depicted in FIG. 2, an analyte sample
52 is introduced via (analyte) input line 54 into an analyte
concentrator assembly 56. Analyte concentrator assembly 56 is
configured to retain one or more analyte molecules of interest
contained in analyte sample 52. Accordingly, at least a portion of
the analyte molecule(s) is retained in analyte concentrator
assembly 56, while the fluid sample effluent (e.g., a substantially
analyte-free sample effluent) is discharged from analyte
concentrator assembly 56 via output line 62.
Substantially analyte-free fluid sample effluent discharged from
analyte concentrator assembly 56 is routed (e.g., fluidly) via
output line 62 from analyte concentrator assembly 56 to eluent
generation module 64 (e.g., where the substantially analyte-free
effluent can be used to generate a substantially analyte-free
eluent). Thus, unlike existing systems in which an effluent is
discharged into waste (see FIG. 1), embodiments of the present
disclosure can use the substantially analyte-free effluent to
generate a substantially analyte-free eluent. Accordingly, whereas
existing systems rely on a separate fluid source to generate
eluent; adding to labor costs, decreasing efficiencies, and
resulting in eluent that may contain a substantial amount of the
analyte molecule of interest, embodiments of the present disclosure
route the effluent discharged from an analyte concentrator assembly
specifically designed to retain the analyte molecule of interest
(thereby discharging a substantially analyte-free effluent) into an
eluent generation module to produce a eluent therefrom that is,
likewise, substantially free of the analyte molecule of interest
retained in the analyte concentrator assembly.
As used herein, "substantially analyte-free," "substantially free
of the analyte (molecule(s))," and the like can be used to refer to
a fluid, sample, and/or product having, including, comprising
and/or containing less than or equal to a threshold amount of a
particular analyte (of interest). For instance, the threshold
amount can be measured in terms of molar concentration, mass, etc.
In one embodiment, "substantially analyte-free," "substantially
free of the analyte (molecule(s))," and the like can refer to less
than or equal to nano-molar, pico-molar, femto-molar, atto-molar,
etc. Alternatively, "substantially analyte-free," "substantially
free of the analyte (molecule(s))," and the like can refer to less
than or equal to a value (whole number or decimal value) of
nano-grams, pico-grams, femto-grams, atto-grams, etc. per unit of
volume (e.g., liter, kiloliter, etc.).
The threshold amount can also be measured in terms of
quantity-per-quantity (e.g., parts (analyte) per notation
(reference)). Accordingly, this (set of) pseudo unit(s) can be used
to describe the small values of the analyte concentration (i.e.,
substantially free) in dimensionless quantities or terms (e.g.,
mole fraction, mass fraction, etc.). Specifically, the threshold
can be measured in terms of ppm (parts-per-million, 10.sup.-6), ppb
(parts-per-billion, 10.sup.-9), ppt (parts-per-trillion,
10.sup.-12) and ppq (parts-per-quadrillion), etc.; where parts can
comprise any value (whole number or decimal value). Accordingly,
"substantially analyte-free," "substantially free of the analyte
(molecule(s))," and the like can refer to less than or equal to one
part analyte per billion parts reference. The unit "1 ppb" can be
used for a mass fraction if the analyte is present at one-millionth
of a gram per gram of sample solution, etc. When working with
aqueous solutions, it is common to assume that the density of water
is 1.00 g/mL. Therefore, it is common to equate 1 gram of water
with 1 mL of water. Consequently, ppb corresponds to 1 .mu.g/L
water (or water based fluid, in some instances).
In a further embodiment, eluent generated in eluent generation
module 64 (of or from the analyte sample effluent) can similarly be
routed (e.g., fluidly) via an (eluent) input line 70 from eluent
generation module 64 to analyte concentrator assembly 56, where the
eluent can be used to elute an analyte retained in analyte
concentrator assembly 56.
In at least one further embodiment, the eluted analyte can be
routed (e.g., fluidly) via an (analyte) output line 76 from analyte
concentrator assembly 56 to an analyte detection module 78, where
the analyte can be analyzed (e.g., the presence of the analyte can
be detected, the identity of the analyte can be determined, the
quantity and/or quality of the analyte can be measured, etc.).
After passing through analyte detection module 78, fluid sample can
be discharged via output line 82 to waste 68.
An optional wash fluid can also be introduced into analyte
concentrator assembly 56 via a separate wash fluid input line (not
shown). Alternatively, the wash fluid can be introduced via input
line 54. The wash fluid can comprise a pre-wash (e.g., configured
to remove any foreign and/or undesirable matter from analyte
concentrator assembly 56 and/or to prepare analyte concentrator
assembly 56 to receive analyte sample 52). Alternatively, or in
addition, the wash fluid can comprise a post-wash (e.g., configured
to remove any un-retained sample (e.g., analyte sample fluid or
molecular component thereof)) from analyte concentrator assembly
56. A wash fluid effluent can also be discharged from analyte
concentrator assembly 56 via output line 62. Alternatively, the
wash fluid effluent can be discharged via a separate output line
(not shown). Those skilled in the art will appreciate, however,
that certain embodiment may not include a wash fluid and/or a
washing step as described above. Instead, in some embodiments, the
volume of analyte sample 52, for instance, may be sufficient to
ensure that a suitable amount of analyte sample 52 passes through
analyte concentrator assembly 56, a suitable amount of analyte is
retained by analyte concentrator assembly 56, and/or a suitable
amount of effluent passes out of analyte concentrator assembly 56,
etc.
Output line 62 can optionally include an (effluent) output valve 66
configured to selectively open one of optional lines 62a, 62b, and
62c (and selectively closing the other lines). For instance, output
valve 66 can selectively open line 62a, connecting effluent output
line 62 to eluent generation module 64, while selectively closing
lines 62b and 62c. Alternatively, output valve 66 can selectively
open line 62b, connecting output line 62 to a waste (drain) 68,
while selectively closing lines 62a and 62c. Furthermore, output
valve 66 can selectively open line 62c, connecting output line 62
to an effluent (purified water/mobile phase) storage member 63,
while selectively closing lines 62a and 62b. In an illustrative
operation, the (substantially analyte-free) sample effluent passing
out of analyte concentrator assembly 56 via effluent output line 62
can be selectively routed via line 62a to eluent generation module
64 or via line 62c to storage member 63. Effluent stored in storage
member 63 can be routed via line 62d to eluent generation module
64. In some embodiments, effluent stored in storage member 63 can
be useful in a variety of other applications, such as making
(generating) standards free from analyte ions using the stored
effluent as a diluent (which can be either done offline
volumetrically or inline via a flowing stream). Similarly, the
optional wash fluid effluent (e.g., substantially analyte-free wash
fluid effluent) passing out of analyte concentrator assembly 56
(e.g., via effluent output line 62) can be selectively routed via
line 62a to eluent generation module 64 or via line 62c to storage
member 63 (e.g., to generate additional substantially analyte-free
eluent and/or to wash the eluent generation module 64).
Alternatively, the wash fluid effluent passing out of analyte
concentrator assembly 56 via effluent output line 62 can be
selectively routed via line 62b to waste 68.
Eluent line 70 can also optionally include a valve 72 (e.g., eluent
valve) configured to selectively open one of optional lines 70a and
70b (and selectively closing the other line). For instance, valve
72 can selectively open line 70a, connecting input line 70 to
analyte concentrator assembly 56, while selectively closing line
70b. Alternatively, output valve 72 can selectively open line 70b,
connecting eluent line 70 to an optional storage member 74, while
selectively closing line 70a. In an illustrative operation, the
substantially analyte-free eluent can pass out of eluent generation
module 64 via eluent line 70 and can be selectively routed via line
70b to optional storage 74.
Storage 74 can comprise a receptacle in some embodiments.
Accordingly, the substantially analyte-free eluent can be stored in
the receptacle for later use. For instance, a line 70c connects
storage 74 to analyte concentrator assembly 56. Accordingly,
substantially analyte-free eluent can pass out of storage 74 and
into analyte concentrator assembly 56 to elute the retained
analyte. Storage 74 can overcome a potential problem in the
configuration of system 50. Specifically, analyte concentrator
assembly 56 may not be prepared (e.g., sufficiently washed, etc.)
to receive the eluent at the time it is discharged from eluent
generation module 64 in some embodiments and/or applications (e.g.,
during a certain run or assay). Thus, storage 74 can provide a
delay sufficient to provide time necessary to (fully) prepare
analyte concentrator assembly 56 prior to introducing the eluent
therein.
Alternatively, eluent line 70 can be configured to provide a
sufficient delay in delivering the eluent to analyte concentrator
assembly 56. For instance, eluent line 70 can include a sample
loop, as known in the art. The sample loop can be connected (e.g.,
fluidly) to analyte concentrator assembly 56, can be used to
precisely load a known volume of the sample into the concentrator
column, and/or can provide the delay described above. Such a delay
may be necessary in order to complete the processing of analyte
sample 52 (through analyte concentrator assembly 56) and/or may
potentially eliminate the need for a separate storage 74 and/or
valve 72. Alternatively, the substantially analyte-free eluent can
pass out of eluent generation module 64 via eluent line 70 and can
be selectively routed via line 70a into analyte concentrator
assembly 56 to elute the retained analyte.
Output line 76 can also optionally include a valve 80 (e.g., eluted
analyte valve) configured to selectively open one of optional lines
76a and 76b (and selectively closing the other line). For instance,
valve 80 can selectively open line 76a, connecting output line 76
to analyte detection module 78, while selectively closing line 76b.
Alternatively, output valve 80 can selectively open line 76b,
connecting output line 76 to waste 68, while selectively closing
line 76a. In an illustrative operation, the eluted analyte can pass
out of analyte concentrator assembly 56 via output line 76 and can
be selectively routed via line 76a to analyte detection module 78.
On the other hand, a wash fluid flowing through system 50 can pass
out of analyte concentrator assembly 56 via output line 76 and can
be selectively routed via line 76b to waste 68.
Output line 82 can also optionally include an output valve 84
configured to selectively open one of optional lines 82a and 82b
(and selectively closing the other line). For instance, valve 84
can selectively open line 82a, connecting output line 82 to waste
68, while selectively closing line 82b. Alternatively, output valve
84 can selectively open line 82b, connecting output line 82 to
analyte detection module 78, while selectively closing line 82a. In
an illustrative operation, fluid sample can be recirculated back
into at least a portion of analyte detection module 78 through a
line 82b (to regenerate one or more components thereof).
Recirculated sample can be discharged from analyte detection module
78 via an output line 86. Output line 86 can also optionally
include an output valve 88 configured to selectively open one of
optional lines 86a and 86b (and selectively closing the other
line). For instance, valve 88 can selectively open line 86a,
connecting output line 86 to waste 68, while selectively closing
line 86b. Alternatively, output valve 88 can selectively open line
86b, connecting output line 86 to elution generation module 64,
while selectively closing line 86a. In an illustrative operation,
fluid sample can be recirculated back into at least a portion of
elution generation module 64 (to regenerate one or more components
thereof).
Those skilled in the art will appreciate that different embodiments
of system 50 can comprise different combinations of the components
described above and/or illustrated in FIG. 2. Accordingly, system
50 according to one or more specific embodiments need not include
each and every component described above and/or illustrated in FIG.
2. Similarly, a variety of methods described herein can involve
passing one or more fluid samples through system 50 or one or more
components thereof. Accordingly, such methods (or other methods)
need not include each and every step described above and/or
illustrated in FIG. 2.
Furthermore, various components of system 50 and/or methods
involving the same (or other methods) will be discussed in further
detail below. It will likewise be appreciated that such components
and/or method steps are illustrative only and that various
embodiments can include more than or fewer than the described
and/or illustrated components and/or method steps.
FIG. 3 depicts a more specific illustrative analyte concentrator
assembly 56a useful in an illustrative system 50 (e.g., which can
be used as analyte concentrator assembly 56--see e.g., FIG. 2). As
depicted in FIG. 3, analyte concentrator assembly 56a comprises an
analyte concentrator 90 having an inlet opening 92 and an outlet
opening 94. Alternatively, analyte concentrator 90 can have a
plurality of inlet openings 92 and/or a plurality of outlet
openings 94. Analyte concentrator assembly 56a further comprises an
optional inlet valve 96, selectively coupling inlet opening 92 of
analyte concentrator 90 to (analyte sample) input line 54 and/or
(eluted analyte sample) output line 76 (as similarly illustrated in
FIG. 2). In addition, analyte concentrator assembly 56a comprises
an optional outlet valve 98, selectively coupling outlet opening 94
of analyte concentrator 90 to (effluent) output line 62 and/or
(eluent) input line 70 (as similarly illustrated in FIG. 2).
Accordingly, analyte concentrator 90 may only require a single
inlet opening 92 and/or a single outlet opening 94 in certain
embodiments.
In some embodiments, analyte concentrator 90 can comprise a
concentrator column (e.g., as known in the art). Such concentrator
columns can have and/or comprise an encircling side wall 90a
extending from a first end 90b of the concentrator column 90 to an
opposing second end 90c of the concentrator column 90 and at least
partially bounding an internal cavity 90d. Such concentrator
columns 90 can also have and/or comprise inlet opening 92 disposed
at the first end 90b and in fluid communication with the internal
cavity 90d and outlet opening 94 disposed at the second end 90c and
in fluid communication with the internal cavity 90d.
Regardless of specific components and/or configurations, analyte
concentrator assembly 56a can have and/or include at least one
analyte retention mechanism 91. For instance, analyte concentrator
column 90 can, illustratively, be and/or comprise an ion
exchange-type concentrator column. Such ion-exchange concentrator
columns 90 can have and/or include an analyte retention mechanism
91 disposed within internal cavity 90d. In at least one embodiment,
analyte retention mechanism 91 can comprise ion-exchange
chromatography material (e.g., resin, polymeric substrate, agarose,
beads, and/or other suitable chromatography material). A typical
ion-exchange concentrator column 90 is packed with the
chromatography material such that the material is disposed and/or
retained therein (e.g., in the internal cavity 90d thereof). Such
material can be configured to carry a net charge (e.g., in one or
more (specific) pH solutions). Electrostatic interactions between
the net charged chromatography material and charged analyte
molecules can cause the chromatography material to retain (e.g.,
bind to) the analyte molecules. Salt and/or acid concentration in
solution can be used to manipulate the chromatography material into
binding or releasing certain types of molecules of interest.
Thus, ion exchange-type concentrator columns 90 can be configured
to retain one or more molecular component(s) based on one or more
ionic and/or charge-related characteristics thereof (e.g., ionic
state in a particular pH of solution). Specifically, some (anionic)
concentrator columns 90 can be configured to retain certain
negatively-charged (anionic) molecules with positively-charged
chromatography material. Accordingly, one or more anionic analytes
disposed in a fluid sample may be retained in the column, while the
fluid sample effluent is discharged from the column. Alternatively,
some (cationic) concentrator columns can be configured to retain
certain positively-charged (cationic) molecules with
negatively-charged chromatography material. Accordingly, one or
more cationic analytes disposed in a fluid sample may be retained
in the column 90, while the fluid sample effluent is discharged
from the column. Other types of concentrator columns 90 are also
known in the art and contemplated herein.
Indeed, a wide variety of analyte concentrator assemblies 56a
and/or analyte concentrators 90 can be configured to retain one or
more molecular component(s) based on specific chemical and/or
structural properties. Each can include an analyte retention
mechanism(s) 91 specifically configured to retain one or more
analyte molecules of interest while allowing the sample effluent to
be discharged. Accordingly, a variety of analyte retention
mechanisms 91 are known in the art and contemplated herein.
Those skilled in the art will appreciate that analyte concentrator
90, as depicted in FIG. 3, can also be preferably configured for
counter-current elution. Specifically, (eluent) input line 70 is
(selectively, fluidly) connected to analyte concentrator 90 via
outlet opening 94 (similar and/or adjacent to (effluent) output
line 62), and (eluted analyte sample) output line 76 is
(selectively, fluidly) connected to analyte concentrator 90 via
inlet opening 92. Accordingly, as discussed in further detail
below, an analyte sample 52 (see e.g., FIG. 2) may be introduced
into and flow through analyte concentrator 90 in a first fluid
direction 93a (e.g., from inlet opening 92 toward outlet opening
94), while an eluted concentrated analyte sample may be eluted and
discharged from analyte concentrator 90 in a second fluid direction
93b (e.g., from outlet opening 94 toward inlet opening 92).
Alternative embodiments can be configured for uniform current flow
operation without departing from the scope of this disclosure.
In at least one embodiment, the volume of eluent introduced into
analyte concentrator 90 (via port 94 and/or to elute an analyte
retained therein) can be substantially less that the volume of the
original analyte sample 52 introduced into analyte concentrator
assembly 56a and/or analyte concentrator 90 thereof (via inlet 92)
during a specific run or assay. Accordingly, the eluted analyte
sample can be significantly concentrated relative to the original
analyte sample. For instance, the eluted analyte sample can be at
least, up to, greater than, about, or between 2-fold, 5-fold,
10-fold, 20-fold, 50-fold, 100-fold, 200-fold, 500-fold, 1000-fold,
10,000-fold, 100,000-fold, or more concentrated relative to the
original analyte sample. In some embodiments, for example, analyte
concentrator 90 (or the analyte retention mechanism 91 thereof) can
initially retain analyte molecules adjacent to inlet opening 92.
Accordingly, the retained analytes can elute from analyte
concentrator 90 in an eluent volume significantly less than the
total volume of the original analyte sample. Thus, the eluted
analyte sample can be or comprise a concentrated, eluted analyte
sample in some embodiments.
In one or more embodiments, an analyte concentrator assembly can
also include one or more multi-port (master) fluid valves. Such a
fluid valve can coordinate fluid flow through the system 50 (see
e.g., FIG. 2) and/or a concentrator column thereof. In some
embodiments, for instance, a multi-port (master) fluid valve can
coordinate fluid flow in and out of an concentrator column (such as
concentrator column 90 illustrated in FIG. 3) and/or illuminate the
need for more or more of optional valves 66, 72, 80, 84, and
88.
FIGS. 4A and 4B illustrate, schematically, an analyte concentrator
assembly 56b comprising a concentrator column 90 and an
illustrative multi-port (master) fluid valve 100 in a first valve
configuration (FIG. 4A) and a second valve configuration (FIG. 4B).
Fluid valve 100 can also be useful in other embodiments of the
present disclosure. As illustrated in FIGS. 4A and 4B, fluid valve
100 comprises six selectively connectable ports 102 and is
selectively configurable between the first and second valve
configurations (to selectively connect different combinations of
the plurality of ports). Fluid valves having less than six or
greater than six ports are also contemplated herein.
In both the first and second valve configurations (illustrated in
FIGS. 4A and 4B, respectively), inlet opening 92 of analyte
concentrator 90 is fluid coupled with a concentrator inlet port
102a. Similarly, outlet opening 94 of analyte concentrator 90 is
fluid coupled with a concentrator outlet port 102d. As discussed in
further detail below, selective fluid communication between
concentrator inlet port 102a and adjacent ports 102b and 102f
alternates between the first and second valve configurations,
respectively. Accordingly, inlet opening 92 is selectively fluid
connectable with port 102b and with port 102f. Likewise, selective
fluid communication between concentrator outlet port 102d and
adjacent ports 102c and 102e alternates between the first and
second valve configurations, respectively. Accordingly, outlet
opening 94 is selectively fluid connectable with port 102c and with
port 102e.
As depicted in FIG. 4A, in the first valve configuration, analyte
input line 54 is connected to a first fluid inlet port 102b, which
is in fluid communication with concentrator inlet port 102a through
the first fluid path of fluid valve 100 (in the first valve
configuration). Accordingly, because inlet opening 92 of analyte
concentrator 90 is in fluid communication with concentrator inlet
port 102a, analyte input line 54 is in fluid communication with
analyte concentrator 90 in the first valve configuration.
Likewise, in the first valve configuration, effluent output line 62
is connected to a first fluid outlet port 102c, which is in fluid
communication with concentrator outlet port 102d through the first
fluid path of fluid valve 100 (in the first valve configuration).
Accordingly, because outlet opening 94 of analyte concentrator 90
is in fluid communication with concentrator outlet port 102d,
effluent output line 62 is in fluid communication with analyte
concentrator 90 in the first valve configuration.
In operation, in the first valve configuration, an analyte sample
52 (see e.g., FIG. 2) passing through analyte input line 54 is
introduced into fluid valve 100 at first fluid inlet port 102b and
passes (fluidly) within the first internal fluid valve flow path of
fluid valve 100 to concentrator inlet port 102a, and then exits
fluid valve 100 through concentrator inlet port 102a to pass
(fluidly), via an optional valve line 100a, into analyte
concentrator 90 via inlet opening 92. As described above, analyte
molecules disposed in the analyte sample (52) are retained in
analyte concentrator 90 by means of one or more analyte retention
mechanisms (91). The substantially analyte-free sample effluent
(i.e., un-retained fluid sample and/or flow-through) passes
(fluidly) out of analyte concentrator 90 via outlet opening 94. The
effluent is then introduced into fluid valve 100 at concentrator
outlet port 102d via an optional valve line 100b. The effluent then
passes (fluidly) within the first internal fluid valve flow path of
fluid valve 100 to first fluid outlet port 102c, and then exits
fluid valve 100 through fluid outlet port 102c to pass (fluidly)
through effluent output line 62 (e.g., to eluent generation module
64 as depicted in FIG. 2).
In the first valve configuration, the first internal fluid flow
path also includes a fluid connection between second fluid inlet
port 102e and second fluid outlet port 102f. Accordingly, a fluid
passing through eluent line 70 is introduced into fluid valve 100
at second fluid inlet port 102e. The fluid then passes (fluidly)
within the first internal fluid flow path of fluid valve 100 to
second fluid outlet port 102f, and then exits fluid valve 100
through second fluid outlet port 102f to pass (fluidly) through
output line 76 (e.g., to waste 68 or analyte detection module 78 as
depicted in FIG. 2). Accordingly, fluid delivered to fluid valve
100 via port 102e (in the first valve configuration) bypasses
analyte concentrator 90 and passes directly to output line 76.
However, as illustrated in FIG. 4B, in the second valve
configuration, (substantially analyte-free eluent) fluid passing
through eluent line 70 (or a sub-line thereof), is introduced into
fluid valve 100 via second fluid inlet port 102e, which is in fluid
communication with opening 94 of analyte concentrator 90 via port
102d and valve line 100b. Accordingly, the substantially
analyte-free eluent exits fluid valve 100 via port 102d and is
introduced into analyte concentrator 90 via valve line 100b (in a
direction opposite the flow of the analyte sample 52 into analyte
concentrator 90 (i.e., in a counter-current direction)). As
indicated above, the substantially analyte-free eluent can be
chemically configured to elute the analyte molecules retained in
analyte concentrator 90 (or by the analyte retention mechanism 91
thereof).
The (concentrated) eluted analyte sample exits analyte concentrator
90 via opening 92 and is introduced into fluid valve 100 at port
102a by means of valve line 100a. The concentrated, eluted analyte
sample then passes to second fluid outlet port 102f via the second
internal fluid flow path of fluid valve 100 (in the second valve
configuration), and then exits fluid valve 100 through second fluid
outlet port 102f to pass (fluidly) through output line 76 (e.g., to
analyte detection module 78 as depicted in FIG. 2).
Furthermore, in the second valve configuration, fluid passing
through line 54 enters fluid valve 100 via first fluid inlet port
102b and passes directly out of fluid valve 100 via the second
internal fluid valve flow path and first fluid outlet port 102c,
and line 62 fluid-coupled therewith.
FIGS. 5A and 5B depict, respectively, flow diagrams of an analyte
concentrator system 50a in a first system configuration (FIG. 5A)
and a second system configuration (FIG. 5B). Like elements between
analyte concentrator system 50a and analyte concentrator system 50
are identified with like reference numerals. Analyte concentrator
system 50a can be configured substantially similar to analyte
concentrator system 50 (see e.g., FIG. 2), with one or more of the
following (or other) described and/or depicted differences. In
particular, analyte concentrator system 50a can include an analyte
concentrator assembly 56c comprising a first concentrator column
90a and a second concentrator column 90b.
As depicted in FIG. 5A, in a first system configuration, analyte
sample 52 is introduced via (analyte) input line 54 into
concentrator column 90a of analyte concentrator assembly 56c. At
least a portion of one or more analyte molecule(s) of interest
contained and/or disposed in analyte sample 52 is retained in
concentrator column 90a, while an analyte sample effluent is
discharged therefrom. The fluid sample effluent discharged from
concentrator column 90a is routed (e.g., fluidly) via output line
62 from analyte concentrator assembly 56c and/or concentrator
column 90a thereof, to eluent generation module 64 (e.g., where the
substantially analyte-free effluent can be used to generate a
substantially analyte-free eluent). Eluent generated in eluent
generation module 64 (of or from the analyte sample effluent) can
similarly be routed (e.g., fluidly) via an (eluent) input line 70
from eluent generation module 64 to analyte concentrator assembly
56c and/or concentrator column 90b thereof, where the eluent can be
used to elute an analyte retained in concentrator column 90b (as
described in further detail below in relation to FIG. 5B).
The analyte eluted from concentrator column 90b is routed (e.g.,
fluidly) via (analyte) output line 76 from analyte concentrator
assembly 56c and/or concentrator column 90b thereof, to an analyte
detection module 78, where the analyte can be analyzed. After
passing through analyte detection module 78, fluid sample can be
discharged via output line 82.
As indicated above, a wash fluid can also be (optionally)
introduced into analyte concentrator assembly 56c and/or
concentrator column 90a thereof via a separate wash fluid input
line (not shown). Alternatively, the wash fluid can be introduced
via input line 54. The wash fluid effluent can also be discharged
from analyte concentrator assembly 56c and/or concentrator column
90a thereof via output line 62. Alternatively, the wash fluid
effluent can be discharged via a separate wash fluid output line
(not shown).
One or more of the valves described previously can also be
incorporated into system 50a, as depicted in FIGS. 5A and 5B, to
alter the flow of fluid sample through system 50a. Recirculation of
analyzed fluid sample can similarly occur as previously described.
In at least one embodiment, a waste line 89 can carry recirculated
or other fluid from eluent generation module 64 to waste 68. In
addition, no fluid sample storage element (such as storage 74
depicted in FIG. 2) is required to operate system 50a effectively
in one or more embodiments. Specifically, no delay is necessarily
required because the eluent generated from the effluent of
concentrator column 90a is introduced into concentrator column 90b
to eluent an analyte already disposed and/or retained therein. Said
analyte is retained in concentrator column 90b as follows.
As depicted in FIG. 5B, in a second system configuration, analyte
sample 52 is introduced via (analyte) input line 54 into
concentrator column 90b of analyte concentrator assembly 56c. At
least a portion of one or more analyte molecule(s) of interest
contained and/or disposed in analyte sample 52 is retained in
concentrator column 90b, while an analyte sample effluent is
discharged therefrom. The fluid sample effluent discharged from
concentrator column 90b is routed (e.g., fluidly) via output line
62 from analyte concentrator assembly 56c and/or concentrator
column 90b thereof, to eluent generation module 64 (e.g., where the
substantially analyte-free effluent can be used to generate a
substantially analyte-free eluent). Eluent generated in eluent
generation module 64 (of or from the analyte sample effluent) can
similarly be routed (e.g., fluidly) via an (eluent) input line 70
from eluent generation module 64 to analyte concentrator assembly
56c and/or concentrator column 90a thereof, where the eluent can be
used to elute an analyte retained in concentrator column 90a (as
described above in relation to FIG. 5A).
The analyte eluted from concentrator column 90a is routed (e.g.,
fluidly) via (analyte) output line 76 from analyte concentrator
assembly 56c and/or concentrator column 90a thereof, to analyte
detection module 78, where the analyte can be analyzed. After
passing through analyte detection module 78, fluid sample can be
discharged via output line 82.
As indicated above, no delay is necessarily required in operating
system 50a because the eluent generated from the effluent of
concentrator column 90b is introduced into concentrator column 90a
to eluent an analyte already disposed and/or retained therein.
Those skilled in the art will again appreciate that different
embodiments of system 50a can comprise different combinations of
the components described above and/or illustrated in FIGS. 5A and
5B. Accordingly, system 50a according to one or more specific
embodiments need not include each and every component described
above and/or illustrated in FIGS. 5A and 5B. Similarly, the method
described above in relation to system 50a can involve passing one
or more fluid samples through one or more components thereof.
Accordingly, such method (or other method) need not include each
and every step described above and/or illustrated in FIGS. 5A and
5B.
As indicated above, an analyte concentrator assembly can also
include one or more multi-port (master) fluid valves. FIGS. 6A and
6B illustrate, schematically, an analyte concentrator assembly 56d
comprising a first concentrator column 90a, a second concentrator
column 90b, and an illustrative multi-port (master) fluid valve 101
in a first valve configuration (FIG. 6A) and a second valve
configuration (FIG. 6B). Fluid valve 100 can also be useful in
other embodiments of the present disclosure. As illustrated in
FIGS. 6A and 6B, fluid valve 101 comprises ten selectively
connectable ports 103 and is selectively configurable between the
first and second valve configurations (to selectively connect
different combinations of the plurality of ports). Fluid valves
having less than ten or greater than ten ports are also
contemplated herein.
In both the first and second valve configurations (illustrated in
FIGS. 6A and 6B, respectively), inlet opening 92a of first analyte
concentrator 90a is fluid coupled with a first concentrator inlet
port 103b. Similarly, outlet opening 94a of first analyte
concentrator 90a is fluid coupled with a first concentrator outlet
port 103e. Likewise, inlet opening 92b of second analyte
concentrator 90b is fluid coupled with a second concentrator inlet
port 103j and outlet opening 94b of second analyte concentrator 90b
is fluid coupled with a second concentrator outlet port 103g.
As discussed in further detail below, selective fluid communication
between first concentrator inlet port 103b and adjacent ports 103a
and 103c alternates between the first and second valve
configurations, respectively. Accordingly, inlet opening 92a of
first analyte concentrator 90a is selectively fluid connectable
with port 103a and with port 103c. Likewise, selective fluid
communication between first concentrator outlet port 103e and
adjacent ports 103f and 103d alternates between the first and
second valve configurations, respectively. Accordingly, outlet
opening 94a is selectively fluid connectable with port 103f and
with port 103d.
Furthermore, selective fluid communication between second
concentrator inlet port 103j and adjacent ports 103i and 103a
alternates between the first and second valve configurations,
respectively. Accordingly, inlet opening 92b of second analyte
concentrator 90b is selectively fluid connectable with port 103i
and with port 103a. Likewise, selective fluid communication between
second concentrator outlet port 103g and adjacent ports 103h and
103f alternates between the first and second valve configurations,
respectively. Accordingly, outlet opening 94b is selectively fluid
connectable with port 103h and with port 103f.
As depicted in FIG. 6A, in the first valve configuration, analyte
input line 54 is connected to a first fluid inlet port 103a, which
is in fluid communication with first concentrator inlet port 103b
through the first internal fluid path of fluid valve 101 (in the
first valve configuration). Accordingly, because inlet opening 92a
of first analyte concentrator 90a is in fluid communication with
concentrator inlet port 103b, analyte input line 54 is in fluid
communication with first analyte concentrator 90a in the first
valve configuration.
Likewise, in the first valve configuration, effluent output line 62
is connected to first fluid outlet port 103f, which is in fluid
communication with first concentrator outlet port 103e through the
first internal fluid path of fluid valve 101 (in the first valve
configuration). Accordingly, because outlet opening 94a of first
analyte concentrator 90a is in fluid communication with
concentrator outlet port 103e, effluent output line 62 is in fluid
communication with first analyte concentrator 90a in the first
valve configuration.
Furthermore, in the first valve configuration, (eluent) input line
70 is connected to a second fluid inlet port 103h, which is in
fluid communication with second concentrator outlet port 103g
through the first internal fluid path of fluid valve 101 (in the
first valve configuration). Accordingly, because outlet opening 94b
of second analyte concentrator 90b is in fluid communication with
second concentrator outlet port 103g, (eluent) input line 70 is in
fluid communication with second analyte concentrator 90b in the
first valve configuration.
Likewise, in the first valve configuration, (eluted analyte sample)
output line 76 is connected to second fluid outlet port 103c, which
is in fluid communication with connector ports 103d, 103i through
the first internal fluid path of fluid valve 101 (in the first
valve configuration). Connector ports 103d, 103i are, in turn, in
fluid communication with second concentrator inlet port 103j
through the first internal fluid path of fluid valve 101 (in the
first valve configuration). Accordingly, because inlet opening 92b
of second analyte concentrator 90b is in fluid communication with
concentrator inlet port 103j, output line 76 is in fluid
communication with second analyte concentrator 90b in the first
valve configuration.
In operation in the first valve configuration, an analyte sample
(52) passing through analyte input line 54 is introduced into fluid
valve 101 at first fluid inlet port 103a, passes (fluidly) within
the first internal fluid valve flow path of fluid valve 101 to
first concentrator inlet port 103b, and then exits fluid valve 101
through first concentrator inlet port 103b to pass (fluidly), via
an optional valve line 101a, into analyte concentrator 90a via
inlet opening 92a. As described above, analyte molecules disposed
in the analyte sample (52) are retained in analyte concentrator 90a
by means of one or more analyte retention mechanisms (91). The
substantially analyte-free sample effluent (i.e., un-retained fluid
sample and/or flow-through) passes (fluidly) out of first analyte
concentrator 90a via outlet opening 94a. The effluent is then
introduced into fluid valve 101 at first concentrator outlet port
103e by means of an optional valve line 101b. The effluent then
passes (fluidly) within the first internal fluid valve flow path of
fluid valve 101 to first fluid outlet port 103f, and then exits
fluid valve 101 through fluid outlet port 103f to pass (fluidly)
through effluent output line 62 (e.g., to eluent generation module
64 as depicted in FIG. 2). Those skilled in the art will appreciate
that an optional wash fluid can also be introduced through input
line 54.
Continuing in the first valve configuration, a fluid eluent (e.g.,
a substantially analyte-free eluent generated of and/or from the
substantially analyte-free effluent of and/or from first
concentrator column 90a in an eluent generation module) passing
through eluent line 70 is introduced into fluid valve 101 at second
fluid inlet port 103h. The eluent then passes (fluidly) within the
first internal fluid flow path of fluid valve 101 (in the first
valve configuration) to second fluid outlet port 103g, and then
exits fluid valve 101 through second fluid outlet port 103g and
passes (fluidly) through an optional valve line 101c to opening 94b
of concentrator column 90b. The eluent elutes at least a portion of
the one or more analyte molecules of interest retained therein (as
described below in relation to FIG. 6B), which is discharged from
column 90b through opening 92b. The eluted analyte is introduced
into fluid valve 101 at port 103j. The first internal fluid flow
path of fluid valve 101 also includes a fluid connection between
ports 103j, 103i, 103d, and 103c. Accordingly, the eluted analyte
sample introduced into fluid valve 101 via port 103j (in the first
valve configuration) passes directly to port 103c and out of fluid
valve 101 via output line 76.
However, as illustrated in FIG. 6B, in the second valve
configuration, the analyte sample (52) passing through analyte
input line 54 and introduced into fluid valve 101 at first fluid
inlet port 103a, passes (fluidly) within the second internal fluid
valve flow path of fluid valve 101 to second concentrator inlet
port 103j, and then exits fluid valve 101 through second
concentrator inlet port 103j to pass (fluidly), via optional valve
line 101d, into analyte concentrator 90b via inlet opening 92b. As
described above, analyte molecules disposed in the analyte sample
(52) are retained in analyte concentrator 90b by means of one or
more analyte retention mechanisms (91). The substantially
analyte-free sample effluent (i.e., un-retained fluid sample and/or
flow-through) passes (fluidly) out of second analyte concentrator
90b via outlet opening 94b. The effluent is then introduced into
fluid valve 101 at second concentrator outlet port 103g by means of
an optional valve line 101c. The effluent then passes (fluidly)
within the second internal fluid valve flow path of fluid valve 101
(in the second valve configuration) to first fluid outlet port
103f, and then exits fluid valve 101 through fluid outlet port 103f
to pass (fluidly) through effluent output line 62 (e.g., to eluent
generation module 64 as depicted in FIG. 2).
Continuing in the second valve configuration, a fluid eluent (e.g.,
substantially analyte-free eluent generated of and/or from the
substantially analyte-free effluent of and/or from second
concentrator column 90b in an eluent generation module) passing
through eluent line 70 is introduced into fluid valve 101 at second
fluid inlet port 103h, which is in fluid communication with opening
94a of first analyte concentrator 90a via ports 103i, 103d, and
103e, as well as optional valve line 101b. Accordingly, the
substantially analyte-free eluent exits fluid valve 101 via port
103e and is introduced into analyte concentrator 90a (in a
direction opposite the flow of the analyte sample (52) into analyte
concentrator 90a (i.e., in a counter-current direction) as
described above in relation to FIG. 6A). The substantially
analyte-free eluent can be chemically configured to elute the
analyte molecules retained in analyte concentrator 90a (or by the
analyte retention mechanism (91) thereof).
The (concentrated) eluted analyte sample exits analyte concentrator
90a via opening 92a and is introduced into fluid valve 101 at port
103b. The concentrated, eluted analyte sample then passes to second
fluid outlet port 103c via the second internal fluid flow path of
fluid valve 101 (in the second valve configuration), and then exits
fluid valve 101 through second fluid outlet port 103c to pass
(fluidly) through output line 76 (e.g., to analyte detection module
78 as depicted in FIG. 5B).
As illustrated in FIG. 8, analyte detection module 78 can comprise
a chromatography member 158, a suppressing member 160, a
conductivity detector 170, and/or a data management member 180 in
one or more embodiments. It will be appreciated, however, that
analyte detection module 78 need not include each of the
aforementioned components and/or can include additional components
as known in the art. Illustratively, in operation, the eluted,
concentrated analyte can pass via line 76 (or sub-line 76a thereof,
see FIG. 2) into chromatography member 158. Chromatography member
158 can comprise, for example, an ion exchange (separation) column,
such as an anion exchange or cation exchange column in certain
embodiments. Such chromatography (separation) columns can be used
to separate (ionic) material eluted off of the analyte concentrator
(column) 90.
The eluted, concentrated (and optionally separated) analyte sample
can pass via line 112 from chromatography member 158 to suppressing
member 160 of analyte detection module 78 in at least one
embodiment. In some embodiments, a suppressing member (i.e.,
"suppressor") can be used to suppress the conductivity of the
eluent and increase the conductivity of the (fully) dissociated
analyte (e.g., before the analyte sample is introduced into a
detection component, such as conductivity detector 170).
Illustratively, suppressing member 160 can be or comprise an
electrolytic suppressor, eluent suppressor, electrolytic eluent
suppressor, electrolytically regenerated suppressor, etc. as known
in the art. Suppressing member 160 can also function and/or be used
to suppress the conductivity of the eluent and increase the
conductivity of the fully dissociated analyte. For instance, in
some embodiments, suppressing member 160 can comprise a suppressing
element 160a or other mechanism suitable for suppressing the
conductivity of the eluent in the fluid sample and increasing the
conductivity of the fully dissociated analyte in the fluid
sample.
The eluted, concentrated analyte can also pass via line 112a from
suppressing member 160 into conductivity detector 170 of analyte
detection module 78 in at least one embodiment. Conductivity
detector 170 can comprise a conductivity cell 170a or other
mechanism suitable for measuring the conductivity of the fluid
sample.
In some embodiments, conductivity detector 170 can communicate
(e.g., wirelessly and/or via physical (wired) connection 112c) with
data management member 180. Data management member 180 can comprise
a computer-implemented software program 180a in certain
embodiments. The software program and be stored on a
computer-readable media 180b in one or more embodiments.
Accordingly, data management member 180 can also include a (general
or special purpose) computer 180c configured to operate the
software program and/or execute the computer-readable media.
In addition, a fluid recycling line 112b can form an additional
connection between suppressing member 160 and conductivity detector
170. Accordingly, in a recycle mode, the measured sample can be
introduced back into suppressing member 160 to regenerate the
suppressing member 160. The sample can then exit suppressing member
160 via line 86 as described above.
As illustrated in FIG. 7, eluent generation module 64 can comprise
a pump 120, an eluent generation component 130, a trap column 140
and/or a de-gasser 150. In operation, a substantially analyte-free
effluent of and/or (discharged) from an analyte concentrator
assembly and/or analyte concentrator column thereof passes via
effluent line 62 and pump 120 into eluent generation component 130
by means of optional line 110a. Pump 120 can be or comprise a
high-pressure, non-metallic fluid pump in one or more
embodiments.
Eluent generation component 130 can include an anode 130a, a
cathode 130b (disposed substantially opposite anode 130a), and an
electrolytic chamber 130c disposed at least partially between anode
130a and cathode 130b. The electrolytic chamber 130c can include an
electrolyte reservoir 130d, an eluent generation chamber 130e,
and/or an ion exchange connector 130f (e.g., disposed between the
electrolyte reservoir 130d and the eluent generation chamber 130e).
In another embodiment, one of the electrodes is disposed in the
electrolyte reservoir 130d and the other electrode is disposed in
the eluent generation chamber 130e.
The substantially analyte-free eluent generated in eluent
generation component 130 passes via optional line 110b to an
optional trap column 140 (e.g., configured to trap any residual
contaminants in the eluent and/or to further purify the eluent). In
at least one embodiment, trap column 140 can be or comprise a
continuously regenerated trap column (CR-TC) as known in the
art.
The substantially analyte-free eluent then optionally passes via
optional line 110c into de-gasser 150. In at least one embodiment,
de-gasser 150 can comprise a gas permeable membrane 150a configured
to remove at least some of any electrolytic gases in the
eluent.
The substantially analyte-free eluent then passes out of eluent
generation module 64 by means of (eluent) line 70 as described
above. In certain embodiments, a recycling and/or regenerating
fluid can enter eluent generation module 64 and/or a component
thereof (e.g., de-gasser 150) by means of line 86 as described
above. For instance, the recycling and/or regenerating fluid can
aid in removing at least some of any electrolytic gases in the
eluent as described above. The fluid can also be optionally routed
to trap column 140 to regenerate the column. The fluid can also be
discharged from eluent generation module 64 and/or a component
thereof (e.g., trap column 140) via line 110d (e.g., into
waste).
Analyte concentrator systems described herein can be operated by
one or more chromatography operating platforms. Operating platforms
can include one or more fluid pumps, valves, lines, and/or control
software programs. For instance, CHROMELEON.TM. chromatography data
systems is offered commercially by Thermo Fisher Scientific for
controlling chromatographic processes along with other types of
analytical instrumentation.
Reference is also made herein to an analyte sample (such as analyte
sample 52). Such an analyte sample can comprise a fluid, such as
substantially potable (drinking) water, illustratively. The sample
may need to be analyzed for the presence of one or more analytes
(or analyte molecules) of interest (e.g., in order to determine the
level(s) of the analyte(s) therein). For instance, drinking water
may need to adhere to specific (governmental) standards, such as
the National Primary Drinking Water Regulations (NPDWRs or primary
standards). However, the concentration of certain analytes may be
difficult to detect without concentrating the analytes prior to
detection.
Analyte concentrator assemblies, such as those described herein,
can include an ionic or ion-exchange concentrator column configured
to retain certain ionic molecules. For instance, a drinking water
sample containing one or more ionic impurities can be introduced
into the concentrator column such that the ions are retained in the
column. By way of illustration, an anionic-exchange concentrator
column can be configured to retain certain negatively-charged
(anionic) molecules contained and/or disposed in the fluid sample.
Accordingly, one or more anionic analytes may be retained in such a
concentrator column, while the fluid sample effluent discharged
therefrom can be substantially free of the one or more anionic
analytes. Alternatively, the concentrator column can comprise a
cationic concentrator column configured to retain certain
positively-charged (cationic) molecules contained and/or disposed
in the fluid sample. Accordingly, one or more cationic analytes may
be retained in such a concentrator column, while the fluid sample
effluent discharged therefrom can be substantially free of the one
or more cationic analytes.
By way of illustration, to accomplish such an elution, the eluent
(such as that generated in an eluent generation module of and/or
from the substantially analyte-free effluent, as described herein)
can include chemical constituents that are more likely to be
retained by the concentrator column than is the analyte.
Accordingly, the analyte molecules of interest are released as the
chemical constituents of eluent are retained instead.
The eluent may be generated manually, by mixing an eluent solution,
or automatically, by an eluent generator. The eluent generator can
process an input fluid to produce an eluent therefrom. For
instance, the eluent generator can process the substantially
analyte-free effluent (e.g., by exchanging molecules disposed
therein with molecules adapted for eluting the retained analyte(s)
from the concentrator column).
Accordingly, various embodiments of the present disclosure overcome
or solve one or more of the foregoing or other problems in the art,
by providing a substantially analyte-free eluent, generated of
and/or from the substantially analyte-free effluent of and/or
(discharged) from an analyte concentrator assembly and/or analyte
concentrator column thereof, and configured for eluting analyte(s)
retained in the same or different analyte concentrator assembly
and/or analyte concentrator column thereof. The analyte sample
effluent can also be used as wash fluid (for washing un-retained
fluid sample from the system) in certain embodiments.
The foregoing detailed description makes reference to specific
exemplary embodiments. However, it will be appreciated that various
modifications and changes can be made without departing from the
scope contemplated herein and as set forth in the appended claims.
More specifically, while illustrative exemplary embodiments in this
disclosure have been more particularly described, the present
disclosure is not limited to these embodiments, but includes any
and all embodiments having modifications, omissions, combinations
(e.g., of aspects across various embodiments), adaptations and/or
alterations as would be appreciated by those in the art based on
the foregoing detailed description. The limitations in the claims
are to be interpreted broadly based on the language employed in the
claims and not limited to examples described in the foregoing
detailed description, which examples are to be construed as
non-exclusive.
Moreover, any steps recited in any method or process described
herein and/or recited in the claims may be executed in any order
and are not necessarily limited to the order presented in the
claims, unless otherwise stated (explicitly or implicitly) in the
claims. Accordingly, the scope of the invention should be
determined solely by the appended claims and their legal
equivalents, rather than by the descriptions and examples given
above.
It will also be appreciated that various features, members,
elements, parts, and/or portions of certain embodiments of the
present invention are compatible with and/or can be combined with,
included in, and/or incorporated into other embodiments of the
present invention. Thus, disclosure a certain features, members,
elements, parts, and/or portions relative to a specific embodiment
of the present invention should not be construed as limiting
application or inclusion of said features, members, elements,
parts, and/or portions to the specific embodiment. Rather, it will
be appreciated that other embodiments can also include said
features, members, elements, parts, and/or portions without
necessarily departing from the scope of the present invention.
Likewise, certain embodiments can include fewer features than those
disclosed in specific examples without necessarily departing from
the scope of this disclosure.
In addition, the present invention may be embodied in other
specific forms without departing from its spirit or essential
characteristics. The described embodiments are to be considered in
all respects only as illustrative and not restrictive. The scope of
the invention is, therefore, indicated by the appended claims
rather than by the foregoing description. All changes which come
within the meaning and range of equivalency of the claims are to be
embraced within their scope.
* * * * *